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Gene knockout of Zmym3 in mice arrests spermatogenesis at meiotic metaphase with defects in spindle assembly checkpoint

ABSTRACT: To elucidate the molecular bases for the infertile phenotype of Zmym3 KO mice at the mRNA expression level, we carried out RNA sequencing (RNA-seq) analysis on cultured spermatogonial stem cells (SSCs), c-KIT+ pre-meiotic cells induced from SSCs and spermatocytes directly isolated from adult mouse testes.

ORGANISM(S): Mus musculus

PROVIDER: GSE99076 | GEO | 2017/05/19

SECONDARY ACCESSION(S): PRJNA387186

REPOSITORIES: GEO

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Gene knockout of Zmym3 in mice arrests spermatogenesis at meiotic metaphase with defects in spindle assembly checkpoint.

Project description:ZMYM3, a member of the MYM-type zinc finger protein family and a component of a LSD1-containing transcription repressor complex, is predominantly expressed in the mouse brain and testis. Here, we show that ZMYM3 in the mouse testis is expressed in somatic cells and germ cells until pachytene spermatocytes. Knockout (KO) of Zmym3 in mice using the CRISPR-Cas9 system resulted in adult male infertility. Spermatogenesis of the KO mice was arrested at the metaphase of the first meiotic division (MI). ZMYM3 co-immunoprecipitated with LSD1 in spermatogonial stem cells, but its KO did not change the levels of LSD1 or H3K4me1/2 or H3K9me2. However, Zmym3 KO resulted in elevated numbers of apoptotic germ cells and of MI spermatocytes that are positive for BUB3, which is a key player in spindle assembly checkpoint. Zmym3 KO also resulted in up-regulated expression of meiotic genes in spermatogonia. These results show that ZMYM3 has an essential role in metaphase to anaphase transition during mouse spermatogenesis by regulating the expression of diverse families of genes.

| S-EPMC5520888 | biostudies-literature

ZMYM3 is required for the role of KDM1A in HCC cells [97H_KDM1A_shZMYM3_CUTTag_seq]

Project description:To investigate the relationship between KDM1A and ZMYM3, we conducted CUT&Tag-seq experiments to detect the DNA binding regions of KDM1A in HCC cells with ZMYM3 downregulation.

2024-05-31 | GSE228069 | GEO

ZMYM3 is required for KDM1A-mediated histone de-methylation in HCC cells

Project description:To investigate the relationship between KDM1A and ZMYM3, we conducted CUT&Tag-seq experiments to detect the KDM1A-mediated histone de-methylation in HCC cells with ZMYM3 downregulation.

2024-05-31 | GSE228255 | GEO

Kaiso, a critical regulator of spermatogenesis

Project description:Spermatogenesis is a highly coordinated process by which diploid spermatogonia (2n) differentiate into mature haploid (1n) spermatozoa in the seminiferous epithelium. Here, we show that Kaiso (Zbtb33) is critical to spermatogenesis, via binding to KBEs (Kaiso-binding elements) in the 5’ upstream regulatory regions of Gdnf and Plzf to repress their expression, promoting the differentiation of spermatogonial stem cells (SSCs). In Kaiso-/Y mice, Plzf and Gdnf were derepressed in both SSCs and Sertoli cells, explaining the increased number of SSCs observed in these abnormal mice. We also found that Bcl6, an antiapoptotic spermatocyte survival factor, represses the Crem pathway genes. In particular, Kaiso represses Bcl6 by binding two KBEs in the Bcl6 5’ upstream regulatory region and first intron, thus indirectly derepressing Crem and Crem pathway genes. In Kaiso-/Y mice, Bcl6 is overexpressed, and these mice lack differentiated post-mitotic cells and consequently, are infertile. Interestingly, epigenetic “marks,” histone post-translational modifications such as lysine methylation, within histone H3 (H3K27me3), of the promoters of Kaiso target genes, were found transgenerationally heritable, prior to “wash out” during generations 1-3 in Kaiso-/Y mice, thus impacting Kaiso target gene expression. Consequently, Kaiso, by repressing Plzf, Gdnf, and Bcl6, indirectly upregulates Crem, and thereby plays a critical role not only in SSC differentiation, but also in post-meiotic events during spermatogenesis.

2021-03-05 | GSE111409 | GEO

Multiomics Approach to Profiling Development of the Spermatogonial Stem Cell Niche Focused on Sertoli cell Maturation

Project description:Spermatogonial stem cells are the foundation of spermatogenesis and as such can serve as a tool for the treatment of infertility in prepubertal cancer survivors. Spermatogonial stem cells are unique as they develop from primordial germ cells (PGCs), which colonize the developing tubules as immature SSC precursors. It has been controversial, when SSCs are maturing to an adult-like stem cell and recent research has found that prepubertal SSCs are actually metabolically distinct from adult SSCs until puberty. Sertoli cells picture a major part of the SSC niche and undergo drastic changes with puberty and polarize to compartmentalize the seminiferous epithelium with formation of tight junctions to a tight basal part where SSCs reside and an apical part with more differentiated stages of spermatogenesis. In the study were mapping the progression of Sertoli cells maturation events to the metabolic changes SSCs undergo during prepubertal development.

2023-02-24 | PXD037764 | Pride

Testis single-cell RNA-sequencing in the cynomolgus macaque reveals conserved transcriptional profiles during mammalian spermatogenesis

Project description:Spermatogenesis in mammals is a complex and highly orchestrated process, which involves the differentiation of diploid (2n-DNA content) spermatogonia into haploid (n) sperm. This process begins with spermatogonia, a niche of stem cells, which drive this process. Spermatogonial stem cells (SSCs) undergo mitotic self-renewal to maintain this niche, while sub-populations of spermatogonia progressively undergo differentiation and later gain competence to initiate meiosis and form sperm. SSCs undergo extensive chromatin remodelling and major morphological changes, while maintaining genome integrity and parental imprints. To study this in greater detail we performed single-cell RNA sequencing of spermatogenic cells derived from the testis of the non-human primate Macaca fascicularis.

2020-08-13 | E-MTAB-8979 | biostudies-arrayexpress

Transcriptome profiles of seminiferous tubes on different stage of spermatogenesis

Project description:In order to get the different gene expression profiles of these seminiferous tubules on different stages of spermatogenesis, four groups of samples were taken in accordance with the differentiation stage of germ cells, namely: empty tubes before SSCs transplantation (named as “EmptBtrans”), empty tubes after SSCs transplantation (named as “EmptAtrans”), tubes which SSCs had successfully homed and differentiated into spermatocytes and round spermatids (named as “SM_and_RS”) and fluorescent tubes which were taken from recipient mice that already had offsprings to make sure these tubes had complete spermatogenesis (named as “sperm”). Pairwise comparison was made between these four groups, the number of significantly differentially expressed genes increased with the differentiation of germ cells.

2018-12-25 | GSE93327 | GEO

Active enhancer landscape during spermatogenesis.

Project description:Active enhancers are identified by H3K27ac ChIP-seq analysis. To determine the dynamics of active enhancers during spermatogenesis, we performed H3K27ac ChIP-seq and detected reagions of active enhancers during spermatogenesis. We analyzed four representative stages of spermatogenesis: Thy1+ undifferentiated spermatogonia, which contains spermatogonial stem cells and progenitor cells; c-Kit+ differentiating spermatogonia from P7 testes; purified pachytene spermatocytes (PS) undergoing meiosis; and postmeiotic round spermatids (RS) from adult testes.

2020-05-02 | GSE130652 | GEO

ATAC-seq analyses during spermatogenesis

Project description:To determine the dynamics of open chromatin at a genomic resolution during spermatogenesis, we performed ATAC-seq and detected genomic regions of accessible chromatin by Tn5 transposase during spermatogenesis. We analyzed four representative stages of spermatogenesis: Thy1+ undifferentiated spermatogonia, which contains spermatogonial stem cells and progenitor cells; c-Kit+ differentiating spermatogonia from P7 testes; purified pachytene spermatocytes (PS) undergoing meiosis; and postmeiotic round spermatids (RS) from adult testes

2017-10-18 | GSE102954 | GEO

FGF2-regulated gene expression in cultured mouse spermatogonial stem cells

Project description:Transcriptional profiling of mouse spermatogonial stem cells (SSCs) comparing control untreated SSCs with SSCs with exogenous FGF2 withdrawn and FGFR inhibitor SU5402 supplemented (-F+S). Results provide insight into the mechanisms of FGF2-supported in vitro self-renewal of SSCs. Two-condition experiment, SSCs-F+S vs. SSCs. Biological replicates: 4 control replicates, 4 -F+S replicates.

2010-08-01 | E-GEOD-21294 | biostudies-arrayexpress

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